Dental composition

ABSTRACT

Dental composition comprising 
     (a) at least two di- or polyepoxides having 2 to 5 epoxide groups and having a molecular weight of from 200 to 700 Da, or a macromonomeric reaction product obtainable by reacting the diepoxide with a dicarboxylic acid in a molar ratio [diepoxide]/[dicarboxylic acid] of at least 2;
 
(b) one or more primary monoamines and/or disecondary diamines;
 
(c) optionally one or more aliphatic polyamines;
 
(d) a particulate filler,
 
wherein the molar ratio of epoxide groups in component (a) to the N—H bonds in component (b) and (c) [epoxide (a) ]/[N—H (b),(c) ] is in the range of from 0.9 to 1.1;
 
wherein the di- or polyepoxide having 2 to 5 epoxide groups is a compound of the following formula (I):
 
       A(BZ m ) n   (I)
 
     wherein
 
A represents an n-valent organic moiety optionally having 1 to 10 heteroatoms selected from oxygen atoms and sulfur atoms; and
 
B represents an m+1-valent organic moiety,
 
Z is an epoxide group which may have a substituent,
 
m which are independent from each other represent an integer of at least 1; and
 
n is an integer of from 1 to 5;
 
wherein the m are selected so that 2 to 5 epoxide groups are present;
 
wherein the composition does not contain any 2,2-bis-(4-hydroxyphenyl)-propane, or 2,2-bis-(4-hydroxyphenyl)-methane.

FIELD OF THE INVENTION

The present invention relates to a dental composition which does notcontain any bisphenol-A or bisphenol-F, or preferably even an estrogenmimicking derivative thereof. Moreover, the present invention relates toa process for preparing a composition according to the presentinvention. Finally, the present invention relates to a di- orpolyepoxide having 2 to 5 epoxide groups obtainable by the processaccording to the present invention.

The dental composition according to the present invention isparticularly useful as a root canal sealing composition or a pulpcapping composition. According to the present invention, a specific di-or polyepoxide component is used in an epoxide/amine polymerizationsystem. The specific di- or polyepoxide contained in the dentalcomposition according to the present invention may be used for avoidingbisphenol-A or bisphenol-F based components such as bisphenol-Adiglycidyl ether or bisphenol-F diglycidyl ether in a root canal sealingcomposition or pulp capping composition due to favourable mechanicalproperties of the cured compositions and the low viscosity of theuncured compositions, as well as the small dimensional changes of thecompositions upon curing. Advantageously, the specific di- orpolyepoxide contained in the dental composition according to the presentinvention may also provide short gel times.

BACKGROUND OF THE INVENTION

Dental compositions for endodontic purposes are desired to approachnatural tooth structure with regard to physical properties andbiocompatibility. Moreover, good handling properties are also desired.Accordingly, a great effort is documented by the prior art directed tothe development of dental compositions for endodontic purposes, whichhave improved properties with regard to physical properties,biocompatibility, and handling properties.

In the case of a dental root canal sealing composition, the mainobjective is to achieve a high degree of tightness of the root canalfilling. The quality of the root canal filling directly depends on theshrinkage upon setting and the solubility of the material used, as theseproperties are decisive for the impermeability of the treated rootcanal.

Moreover, a low viscosity of the composition is required in order toallow penetration of the composition into the dentin of the root canaland in order to facilitate the complete filling of the root canalincluding any cavities which could not be accessed by a high viscositycomposition with insufficient flow properties. Moreover, in order tomaintain a tight seal, the dental root canal sealing composition shouldhave good adhesion to hard dental structure including dentin.

Dental compositions selected from a root canal sealing composition and apulp capping composition are subject to additional requirements in thatthe cured product is required to have a high radioopacity. The contrastof the material in the root canal as observed by x-ray diagnosticmethods permits conclusions regarding the quality of the filling.Accordingly, a particulate filler having high radioopacity isincorporated into the composition. Suitable filler materials have a highdensity and are prone to settle out from the dental composition duringstorage which gives rise to a stability problem of the composition whichis aggravated when the viscosity of the composition is low. Therefore, adilemma exists between to the viscosity of the composition and thestorage stability of the composition. Furthermore, the storage stabilitymay also be limited in case of precipitation of solid componentsdissolved or dispersed in the dental composition.

Moreover, dental compositions selected from a root canal sealingcomposition and a pulp capping composition that the composition arerequired to be curable in the absence of light. In order to be able tocure a root canal sealing composition or pulp capping composition in theabsence of light, the composition is cured by a thermal curing mechanismwhich may involve step growth polymerizing epoxide precursor compoundssuch as bisphenol-A diglycidylether or bisphenol-F diglycidylether withamine precursors. Bisphenol-A diglycidyl ether or bisphenol-Fdiglycidylether provide an excellent combination of properties for thepurpose of a dental compositions including a favourable gel time instep-growth polymerizations with a diamine or polyamine. Moreover,favourable mechanical properties of the cured compositions while theviscosity of the uncured compositions may be adjusted to be comparablylow, and a low shrinkage of the compositions upon curing are reasons forthe widespread use of bisphenol-A or bisphenol-F diglycidylether basedmaterials in the dental field.

From the prior art, a dental root canal sealer is known which consistsof a paste-paste system AH Plus®. A first paste contains a diepoxide,calcium tungstate, zirconium oxide, aerosil, and a pigment. A secondpaste contains 1-adamantane amine, N,N′-dibenzyl-5-oxa-nonandiamine-1,9,TCD-diamine, calcium tungstate, zirconium oxide, aerosil, silicone oil.The composition cures in a step growth polyaddition reaction into athermoplastic material. The polyaddition reaction of AH Plus® requiresseveral hours whereby the gel time is about 16 hours.

Bisphenol-A and also bisphenol-F are known endocrine disrupters whichcan mimic estrogen and may lead to negative health effects. Inparticular, bisphenol A mimics the structure and function of the hormoneestradiol with the ability to bind to and activate the same estrogenreceptor as the natural hormone. Based on the functional relevance ofbisphenol-A it is considered that bisphenol-A might contribute to thedevelopment of breast cancer. Accordingly, regulatory bodies mightdetermine safety levels of bisphenol-A for humans so that the use ofbisphenol-A based materials containing bisphenol A in a dentalcomposition cannot be continued in the future.

At present, any of the commercially available root canal sealers basedon epoxide-amine chemistry contain bisphenol-A diglycidylether (DGEBA):AH Plus® (DENTSPLY), AH 26 (DENTSPLY), Asphaline® (Alfred Becht GmbH),Acroseal® (Septodont), Adseal® (META BIOMED), Perma Evolution® (METABIOMED), EZ-Fill® (Essentail Dental Systems).

WO 2013/120610 discloses a curable filler material mixture, comprisingan epoxy as component (a), an amine as component (b), and a quaternaryammonium salt as component (c). The mixture contains a single epoxy ascomponent (a), which may be resorcinol diglycidyl ether.

SUMMARY OF THE INVENTION

Accordingly, it is the problem of the present invention to provide adental composition including a root canal sealing composition and a pulpcapping composition, having properties including physical properties ofthe cured composition, dispersion stability and handling properties ofthe uncured composition, and biocompatibility, which are at least on thelevel of corresponding bisphenol-A or bisphenol-F based materials, whilethe composition does not contain any 2,2-bis-(4-hydroxyphenyl)-propane,2,2-bis-(4-hydroxyphenyl)-methane. Preferably, the dental compositionsdo not contain even an estrogen mimicking derivative of2,2-bis-(4-hydroxyphenyl)-propane, or 2,2-bis-(4-hydroxyphenyl)-methane.Moreover, the compositions should have a reduced gel time and provideadhesion to the dentin of a dental root canal in order to furtherimprove the tight sealing of a root canal.

It is a further problem of the present invention to provide a processfor preparing the dental composition including a root canal sealingcomposition and a pulp capping composition, which is economic andtechnically realisable and which may be carried out on a scale which isindustrially relevant for the preparation of a dental composition.

Finally, it is the problem of the present invention to provide apolymerizable compound obtainable in the process of the presentinvention as well as a use of the polymerizable compound for thepreparation of a dental composition.

According to a first aspect, the present invention provides a dentalcomposition comprising

-   (a) at least two di- or polyepoxides having 2 to 5 epoxide groups    and having a molecular weight of from 200 to 700 Da, or a    macromonomeric reaction product obtainable by reacting the diepoxide    with a dicarboxylic acid in a molar ratio [diepoxide]/[dicarboxylic    acid] of at least 2;-   (b) one or more primary monoamines and/or disecondary diamines;-   (c) one or more aliphatic polyamines;-   (d) a particulate filler,    -   wherein the molar ratio of epoxide groups in component (a) to        the N—H bonds in component (b) and (c) [epoxide(a)]/[N—H(b),(c)]        is in the range of from 0.9 to 1.1; wherein the di- or        polyepoxide having 2 to 5 epoxide groups is a compound of the        following formula (I):

A(BZ_(m))_(n)  (I)

-   -   wherein    -   A represents an n-valent organic moiety optionally having 1 to        10 heteroatoms selected from oxygen atoms and sulfur atoms; and    -   B represents an m+1-valent organic moiety,    -   Z is an epoxide group,    -   m which are independent from each other represent an integer of        at least 1; and    -   n is an integer of from 1 to 5;    -   wherein the m are selected so that 2 to 5 epoxide groups are        present;    -   wherein the composition does not contain any        2,2-bis-(4-hydroxyphenyl)-propane,        2,2-bis-(4-hydroxyphenyl)-methane, and preferably does not        contain derivatives thereof.

According to a second aspect, the present invention provides a processfor preparing a composition according to the first aspect, whichcomprises reacting one or more compounds having 2 to 5 hydroxyl groupswith epichlorohydrine for preparing a di- or polyepoxide having 2 to 5epoxide groups as defined by the first aspect.

According to a third aspect, the present invention provides a di- orpolyepoxide having 2 to 5 epoxide groups obtainable by the processaccording to any one of the second aspect.

A dental composition according to the present invention may be providedas a root canal sealing composition and a pulp capping compositionhaving properties including physical properties of the curedcomposition, dispersion stability and handling properties of the uncuredcomposition, and biocompatibility, which are at least on the level ofcorresponding bisphenol-A or bisphenol-F based materials, while thecomposition does not contain any 2,2-bis-(4-hydroxyphenyl)-propane,2,2-bis-(4-hydroxyphenyl)-methane or preferably even an estrogenmimicking derivative thereof.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The term “radioopacity” refers to a substance that will not allow X-raysor similar radiation to pass and or thereby allows X-ray visibility.

The term “derivative of 2,2-bis-(4-hydroxyphenyl)-propane,2,2-bis-(4-hydroxyphenyl)-methane” relates to compounds having theability to bind to and activate the same estrogen receptor as thenatural hormone. Examples of the derivatives are bisphenol AF (CAS:1478-61-1), bisphenol B (CAS: 77-40-7), bisphenol C (CAS: 79-97-0),alpha,alpha-bis(4-hydroxyphenyl)trichloroethane (CAS: 2971-36-0),bisphenol E (CAS: 2081-08-5), bisphenol F (CAS: 620-92-8), bisphenol M(CAS 13595-25-), bisphenol S (CAS 80-09-1), bisphenol Z (CAS843-55-0),4,4-(hexahydro-4,7-methanoindan-5-ylidene)diphenol (CAS: 1943-97-1),4,4-hydroxybenzophenone (CAS: 611-99-4),2,2-bis(4-hydroxyphenyl)propionic acid (CAS 92549-67-2),2,2-bis(4-hydroxyphenyl)propanol (CAS: 142648-65-5), 4,4′-MBTBT (CAS:118-82-1), and 4,4′-thiobisphenol (CAS: 2664-63-3). In general,derivatives are diols or polyols wherein two phenolic hydroxyl groupsare capable of mimicking the interactions of the same estrogen receptoras estradiol of the following formula:

Estradiol is characterized by a distance between the hydroxyl groups ofabout 10.1 Angstrom. Bisphenol A is characterized by a distance betweenthe hydroxyl groups of 9.0 Angstroms. Preferably, a derivative avoids anarrangement of two hydroxyl groups which facilitates the ability of thederivative to bind to and activate the same estrogen receptor as thenatural hormone.

The present invention provides a dental composition. Preferably, thedental composition is a dental root canal sealing composition or adental pulp capping composition. The composition of the presentinvention does not contain any 2,2-bis-(4-hydroxyphenyl)-propane or2,2-bis-(4-hydroxyphenyl)-methane, or preferably even an estrogenmimicking derivative thereof. Accordingly, the starting materials of thecomposition of the present invention are not prepared by using any2,2-bis-(4-hydroxyphenyl)-propane, or 2,2-bis-(4-hydroxyphenyl)-methaneor preferably even an estrogen mimicking derivative thereof so that thecomposition of the present invention may contain unreacted2,2-bis-(4-hydroxyphenyl)-propane, 2,2-bis-(4-hydroxyphenyl)-methane orderivatives thereof, or so that the composition of the present inventionmay leach out 2,2-bis-(4-hydroxyphenyl)-propane,2,2-bis-(4-hydroxyphenyl)-methane or derivatives thereof due tohydrolytic cleavage of bonds which anchor2,2-bis-(4-hydroxyphenyl)-propane, 2,2-bis-(4-hydroxyphenyl)-methane orderivatives thereof in the cured composition.

The dental composition of the present invention comprises (a) at leasttwo di- or polyepoxides having 2 to 5 epoxide groups. The di- orpolyepoxides have a molecular weight of from 200 to 700 Da. Preferably,the molecular weight is in the range of 250 to 600 Da.

Alternatively, component (a) may be a macromonomeric reaction productobtainable by reacting the diepoxide of the formula (I) with adicarboxylic acid in a molar ratio [diepoxide]/[dicarboxylic acid] of atleast 2. The macromonomeric reaction product is an epoxide cappedmolecule which may take part in the epoxide/amine curing reaction withcomponents (b) and/or (c). The dicarboxylic acid may be selected fromterephthalic acid, isophthalic acid, 2,6-naphthalene dicarboxylic acid,diphenyl-4,4-dicarboxylic acid, oxalic acid, malonic acid, succinicacid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaicacid, sebacic acid, undecanedioic acid, and/or dodecanedioic acid. Thereaction may be carried out according to Otera; Matsuzaki, Synthesis1986, 1019; or Deardorff; Myles Org. Synth. 67, 114, which providesbeta-hydroxyalkyl carboxylates by the treatment of the diepoxide with adicarboxylic acid or the corresponding carboxylate ions in the presenceof a suitable catalyst.

The di- or polyepoxide having 2 to 5 epoxide groups is a compound of thefollowing formula (I):

A(BZ_(m))_(n)  (I)

In formula (I), A represents an n-valent organic moiety optionallyhaving 1 to 10 heteroatoms selected from oxygen atoms and sulfur atoms.The term “organic moiety” in relation to residue A means a moiety whichmay be based in general on a hydrocarbon group having 1 to 50 carbonatoms, preferably 2 to 30 carbon atoms, including aliphatic, alicyclic,or aromatic moieties or a combination thereof. Preferably, the organicmoiety consists of, or contains an aromatic moiety. The organic moietylinks or connects further moieties. Accordingly, the organic moiety hasa valency which corresponds to the number of further moieties. In acompound of formula (I), a A(BZ_(m))_(n), the group A represents ann-valent organic moiety optionally having 1 to 10 heteroatoms selectedfrom oxygen atoms and sulfur atoms. The heteroatoms may form part of acarbon chain of the hydrocarbon group, and/or the heteroatoms may form afunctional group such as a carboxyl group, a hydroxyl group, a thiolgroup, or a keto group. According to a preferred embodiment, wherein theheteroatoms selected from oxygen atoms and sulfur atoms in groups A arepresent in ester bonds, ether bonds, thioester bonds or thioether bonds.According to a preferred embodiment, A contains an aromatic ring.Preferably, A is a 1,3-phenylene derivative.

Examples of aliphatic moieties include alkyl groups. According to theinvention, a C₁₋₂₀ alkyl group can include straight or branched alkylgroups having 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, forexample, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,sec-butyl, tert-butyl, n-pentyl, isopentyl and n-hexyl. Examples of agroup A which is an n-valent aliphatic moiety optionally having 1 to 10heteroatoms selected from oxygen atoms and sulfur atoms, are alkylenegroups, polyoxyalkylene groups such as polyoxyethylene groups orpolyoxypropylene groups. When n is 2, then an aliphatic moiety ispreferably a C₂₋₁₂ alkylene group, more preferably a C₂₋₈ alkylenegroup.

The alicyclic moieties may include, for example, a C₃₋₆ carbocyclicaliphatic ring, a C₃₋₆ heterocyclic aliphatic ring, a C₃₋₆ saturatedaliphatic ring, or a C₃₋₆ unsaturated aliphatic ring. Examples ofalicyclic groups include cycloalkyl or cycloalkylalkyl groups. Acycloalkyl group may be a C₃₋₆ cycloalkyl group. Examples of thecycloalkyl group can include those having 3 to 6 carbon atoms, forexample, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Acycloalkylalkyl group can include those having 4 to 8 carbon atoms.Examples for a cycloalkylalkyl group can include a combination of astraight or branched alkyl group having 1 to 6 carbon atoms and acycloalkyl group having 3 to 6 carbon atoms. Examples of thecycloalkylalkyl group can for example, include methylcyclopropyl,methylcyclobutyl, methylcyclopentyl, methylcyclohexyl, ethylcyclopropyl,ethylcyclobutyl, ethylcyclopentyl, ethylcyclohexyl, propylcyclopropyl,propylcyclobutyl, and propylcyclopentyl. Examples of a group A which isan n-valent alicyclic moiety optionally having 1 to 10 heteroatomsselected from oxygen atoms and sulfur atoms, are polyoxyalkylene groupssuch as polyoxyethylene groups or polyoxypropylene groups.

An aromatic moieties may include a phenyl group or a naphtyl group.Preferred moieties of A include the following structures (i) and (ii):

In view of shortening the gel time of the dental composition of thepresent invention, it is preferred that A is (ii).

It has been found that with identical di- or polyamine components,aromatic glycidyl ethers, e.g. of formula (ii) provide a reduced gellingtime as compared to the corresponding aromatic glycidyl esters, e. g.according to (i).

Specific examples of groups A containing one or more aromatic rings maybe derived from bisphenol AP (CAS: 1571-75-1), bisphenol BP (CAS:1844-01-5), bisphenol FL (CAS: 3236-71-3), bisphenol G (CAS: 127-54-8),bisphenol P (CAS: 2167-51-3), bisphenol PH (CAS: 24038-68-4), bisphenolTMC (CAS: 129188-99-4), alpha,alpha bi-paraphenol (CAS: 6052-84-2), orresorcinol.

In Formula (I), B represents an m+1-valent organic moiety. The term“organic moiety” in relation to residue B relates to a moiety which maybe based in general on a hydrocarbon group having 1 to 30 carbon atoms,preferably 1 to 20 carbon atoms, including aliphatic, alicyclic, oraromatic moieties or a combination thereof. The organic moiety is linkedto a group A. When the group B is linked to an aromatic group A, thenthe connecting functional group may be a phenolic ether group, abenzylic ether group or an ester group. In view of an increase of thegel time, it is preferable that the connecting functional group is aphenolic ether group or a benzylic ether group. According to a morepreferred embodiment, the connecting functional group is a phenolicether group.

The organic moiety links or connects further moieties. Accordingly, theorganic moiety has a valency which corresponds to the number of furthermoieties. In a compound of formula (I), a A(BZ_(m))_(n), the group Brepresents an m+1-valent organic moiety optionally having 1 to 10heteroatoms selected from oxygen atoms and sulfur atoms. The heteroatomsmay form part of a carbon chain of the hydrocarbon group, and/or theheteroatoms may form a functional group such as a carboxyl group, ahydroxyl group, a thiol group, a keto group, an ester group or athioester group.

Examples of aliphatic moieties include alkyl groups. According to theinvention, a C₁₋₂₀ alkyl group can include straight or branched alkylgroups having 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, forexample, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,sec-butyl, tert-butyl, n-pentyl, isopentyl and n-hexyl. Examples of agroup A which is an n-valent aliphatic moiety optionally having 1 to 10heteroatoms selected from oxygen atoms and sulfur atoms, arepolyoxyalkylene groups such as polyoxyethylene groups orpolyoxypropylene groups.

The alicyclic moieties may include, for example, a C₃₋₆ carbocyclicaliphatic ring, a C₃₋₆ heterocyclic aliphatic ring, a C₃₋₆ saturatedaliphatic ring, or a C₃₋₆ unsaturated aliphatic ring. Examples ofalicyclic groups include cycloalkyl or cycloalkylalkyl groups. Acycloalkyl group may be a C₃₋₆ cycloalkyl group. Examples of thecycloalkyl group can include those having 3 to 6 carbon atoms, forexample, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Acycloalkylalkyl group can include those having 4 to 8 carbon atoms.Examples for a cycloalkylalkyl group can include a combination of astraight or branched alkyl group having 1 to 6 carbon atoms and acycloalkyl group having 3 to 6 carbon atoms. Examples of thecycloalkylalkyl group can for example, include methylcyclopropyl,methylcyclobutyl, methylcyclopentyl, methylcyclohexyl, ethylcyclopropyl,ethylcyclobutyl, ethylcyclopentyl, ethylcyclohexyl, propylcyclopropyl,propylcyclobutyl, and propylcyclopentyl. Examples of a group A which isan n-valent alicyclic moiety optionally having 1 to 10 heteroatomsselected from oxygen atoms and sulfur atoms, are polyoxyalkylene groupssuch as polyoxyethylene groups or polyoxypropylene groups

An aromatic moieties may include a phenyl group or a naphtyl group.

Z is an epoxide group which may have a substituent. The substituent maybe selected from a straight chain or branched C₁₋₆ alkyl group.Preferably, Z is an unsubstituted epoxide group.

In a group BZ_(m), a single moiety B carries at least one epoxide groupZ. In case a moiety B carries more than one epoxide group Z, thestructure of the epoxide groups Z, i.e. the presence or absence and thenature of the substituent of the epoxide group are independent from eachother. The epoxide group Z may form part of the main chain of moiety B.Alternatively, the epoxide group Z may be present as an end group of themain chain or a side chain of moiety B. Preferably, a group B does notcontain more than 4 epoxide groups, more preferably a group B contains 1or 2 epoxide groups. Accordingly, m is preferably an integer of from 1to 5, more preferably 1 to 4, still more preferably 1 or 2.

In formula (I), n is an integer of from 1 to 5. Accordingly, in acompound of formula (I), at least one BZ_(m) group is present. Moreover,in a compound of formula (I), at most five BZ_(m) group are present. Ifmore than one BZ_(m) group is present, then the BZ_(m) groups may be thesame or different.

The BZ_(m) groups are selected so that 2 to 5 epoxide groups arepresent. Preferably, a compound of formula (I) has two or three epoxidegroups. According to a preferred embodiment, BZ is a group of theformula (II) or (III):

whereinX is —NH—, an oxygen atom or a sulfur atom,X′ is —NH—, an oxygen atom or a sulfur atom,X″ is —NH—, an oxygen atom or a sulfur atom,X′″ is —CH₂—, —NH—, an oxygen atom or a sulfur atom,R¹¹ and R¹² which may be the same or different, independently representa hydrogen atom or a straight chain or branched C₁₋₆ alkyl group,R¹³ represents a hydrogen atom or a straight chain or branched C₁₋₆alkyl group,R¹⁴ represents a hydrogen atom, a hydroxyl group which may besubstituted, or a straight chain or branched C₁₋₆ alkyl group,o represents an integer of from 2 to 10,p is an integer of from 0, 1 or 2;q which may be the same or different, independently represent an integerof from 0 to 10; v represents an integer of from 1 to 10.

In a group of the formula (II) or (III), p and/or q may be 0.Accordingly, if p is 0, then the group of the formula (II) or (III) doesnot contain an optionally substituted oxyalkylene or polyoxyalkylenespacer moiety. Moreover, if q is 0, then the group of the formula (II)or (III) does not contain an optionally substituted alkylene spacermoiety.

A compound of formula (I) is preferably obtainable by reacting acompound having 2 to 5 hydroxyl groups with epichlorohydrine(1-chloro-2,3-epoxypropane). Preferably, the compound having 2 to 5hydroxyl groups contains phenolic hydroxyl groups.

A compound of formula (I) may be prepared by reacting a compound having2 to 5 hydroxyl groups with epichlorohydrine. The epoxidation reactionof the polyol with epichlorohydrin is known from H. Lee and K. Neville,Handbook of Epoxy Resin, Chap. 2, McGraw-Hill, New York (1967), and P.A. Oyanguren and R. J. J. Williams, Polymer, 33, 2376 (1992) and isbelieved to occur in two steps: in the first step an intermediatechlorohydrin is formed. In a second step, dehydrohalogenation occurswhereby a glycidyl ether is formed.

The following specific compounds of formula (I) may be given:

wherein a and b are integers of at least 1 and n′ is 0 or an integer ofat least 1.

According to a specific embodiment, a combination of an aromatic and anon-aromatic compound of formula (I) is used. Specifically, the aromaticcompound of formula (I) may be compound (Ia), (Ib), and/or (Ic). Thenon-aromatic compound of formula (I) may be compound (Id), in particularcompound (Ie).

The dental composition according to the present invention preferablycomprises two or more di- or polyepoxides having 2 to 5 epoxide groupsin order to prevent precipitation of a di- or polyepoxides from thedental composition. The two or more di- or polyepoxides may be used inabout equimolar amounts in the composition. Alternatively, the two ormore di- or polyepoxides may be used in amounts so that the amounts ofepoxide groups belonging to each compound are present in about equimolaramounts, which differs from equimolar amounts of the di- or polyepoxidesin case of different numbers of epoxide groups per molecule. In general,it is preferred that each of the two or more di- or polyepoxides ispresent in an amount of at least 5 percent by weight, more preferably atleast 10 percent by weight based on the total weight of the di- orpolyepoxides.

The dental composition according to the present invention furthercontains (b) one or more primary monoamines and/or disecondary diamines.Component (b) is reactive with the epoxides of component (a) in anepoxide/amine reaction. A primary monoamines may be a compound of thefollowing formula (IV):

R—NH₂  (IV)

wherein R is a monovalent aliphatic moiety which may be substituted byan aromatic group. However, aromatic amines are not preferred. The term“aliphatic moiety” in relation to residue R relates to a moiety whichmay be based in general on an aliphatic hydrocarbon group having 1 to 30carbon atoms, preferably 1 to 20 carbon atoms, which may contain astraight chain, branched chain, or non-aromatic ring or a combinationthereof, and which is preferably a saturated moiety. The group R mayoptionally contain 1 to 10 heteroatoms selected from oxygen atoms andsulfur atoms. The heteroatoms may form part of a carbon chain, and/orthe heteroatoms may form a functional group such as a hydroxyl group, athiol group, a keto group, an ester group or a thioester group.

Examples of aliphatic moieties include alkyl groups. A C₁₋₂₀ alkyl groupcan include straight or branched alkyl groups having 1 to 20 carbonatoms, preferably 1 to 10 carbon atoms, for example, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl,isopentyl and n-hexyl. Examples of a group R which is an n-valentaliphatic moiety optionally having 1 to 10 heteroatoms selected fromoxygen atoms and sulfur atoms, are polyoxyalkylene groups such aspolyoxyethylene groups or polyoxypropylene groups.

The alicyclic moieties may include, for example, a C₃₋₂₀ carbocyclicaliphatic ring, a C₃₋₂₀ heterocyclic aliphatic ring, a C₃₋₂₀ saturatedaliphatic ring, or a 03-20 unsaturated aliphatic ring. Examples ofalicyclic groups include cycloalkyl or cycloalkylalkyl groups. Acycloalkyl group may be a C₃₋₆ cycloalkyl group. Examples of thecycloalkyl group can include those having 3 to 6 carbon atoms, forexample, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Acycloalkylalkyl group can include those having 4 to 8 carbon atoms.Examples for a cycloalkylalkyl group can include a combination of astraight or branched alkyl group having 1 to 6 carbon atoms and acycloalkyl group having 3 to 6 carbon atoms. Examples of thecycloalkylalkyl group can for example, include methylcyclopropyl,methylcyclobutyl, methylcyclopentyl, methylcyclohexyl, ethylcyclopropyl,ethylcyclobutyl, ethylcyclopentyl, ethylcyclohexyl, propylcyclopropyl,propylcyclobutyl, and propylcyclopentyl. R may also be a polycylic groupsuch as an adamantyl group.

The monovalent aliphatic moiety may be substituted by an aromatic groupsuch as a phenyl group or a naphthyl group.

Examples of a primary monoamine may be selected from benzylamine,2-phenylethylamine, cyclohexylamine, decylamine and dodecylamine.

An disecondary diamine may be a compound of the following formula (V):

R′NHR″NHR′″  (V)

In formula (V), R′ and R″ represent a monovalent aliphatic moiety whichmay be substituted by an aromatic group. R′ and R′″ may be the same ordifferent. The term “aliphatic moiety” in relation to residues R′ andR′″ relates to a moiety which may be based in general on an aliphatichydrocarbon group having 1 to 30 carbon atoms, preferably 1 to 20 carbonatoms, which may contain a straight chain, branched chain, ornon-aromatic ring or a combination thereof, and which is preferably asaturated moiety. The group R′ and R′″ may optionally contain 1 to 10heteroatoms selected from oxygen atoms and sulfur atoms. The heteroatomsmay form part of a carbon chain, and/or the heteroatoms may form afunctional group such as a hydroxyl group, a thiol group, a keto group,an ester group or a thioester group.

Examples of aliphatic moieties include alkyl groups. A C₁₋₂₀ alkyl groupcan include straight or branched alkyl groups having 1 to 20 carbonatoms, preferably 1 to 10 carbon atoms, for example, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl,isopentyl and n-hexyl.

The alicyclic moieties may include, for example, a C₃₋₂₀ carbocyclicaliphatic ring, a C₃₋₂₀ heterocyclic aliphatic ring, a C₃₋₂₀ saturatedaliphatic ring, or a C₃₋₂₀ unsaturated aliphatic ring. Examples ofalicyclic groups include cycloalkyl or cycloalkylalkyl groups. Acycloalkyl group may be a C₃₋₆ cycloalkyl group. Examples of thecycloalkyl group can include those having 3 to 6 carbon atoms, forexample, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Acycloalkylalkyl group can include those having 4 to 8 carbon atoms.Examples for a cycloalkylalkyl group can include a combination of astraight or branched alkyl group having 1 to 6 carbon atoms and acycloalkyl group having 3 to 6 carbon atoms. Examples of thecycloalkylalkyl group can for example, include methylcyclopropyl,methylcyclobutyl, methylcyclopentyl, methylcyclohexyl, ethylcyclopropyl,ethylcyclobutyl, ethylcyclopentyl, ethylcyclohexyl, propylcyclopropyl,propylcyclobutyl, and propylcyclopentyl. R′ and R′″ may also be apolycylic group such as an adamantyl group.

In formula (V), R″ is a divalent aliphatic moiety. The term “aliphaticmoiety” in relation to residue R″ relates to a moiety which may be basedin general on an aliphatic hydrocarbon group having 1 to 30 carbonatoms, preferably 2 to 20 carbon atoms, which may contain a straightchain, branched chain, or non-aromatic ring or a combination thereof,and which is preferably a saturated moiety. The group R″ may optionallycontain 1 to 10 heteroatoms selected from oxygen atoms and sulfur atoms.The heteroatoms may form part of a carbon chain, and/or the heteroatomsmay form a functional group such as a hydroxyl group, a thiol group, aketo group, an ester group or a thioester group.

Examples of aliphatic moieties of R″ include alkylene groups. A C₁₋₂₀alkylene group can include straight or branched alkylene groups having 1to 20 carbon atoms, preferably 1 to 10 carbon atoms, for example,methylene, ethylene, n-propylene, isopropylene, n-butylene, isobutylene,sec-butylene, tert-butylene, n-pentylene, isopentylene and n-hexylene.Examples of a group R″ which is an n-valent aliphatic moiety optionallyhaving 1 to 10 heteroatoms selected from oxygen atoms and sulfur atoms,are polyoxyalkylene groups such as polyoxyethylene groups orpolyoxypropylene groups.

The alicyclic moieties may include, for example, a C₃₋₂₀ carbocyclicaliphatic ring, a C₃₋₂₀ heterocyclic aliphatic ring, a C₃₋₂₀ saturatedaliphatic ring, or a C₃₋₂₀ unsaturated aliphatic ring. Examples ofalicyclic groups include cycloalkylene or cycloalkylalkylene groups. Acycloalkylene group may be a C₃₋₆ cycloalkylene group. Examples of thecycloalkylene group can include those having 3 to 6 carbon atoms, forexample, cyclopropylene, cyclobutylene, cyclopentylene andcyclohexylene. A cycloalkylalkylene group can include those having 4 to8 carbon atoms. Examples for a cycloalkylalkylene group can include acombination of a straight or branched alkylene group having 1 to 6carbon atoms and a cycloalkyl group having 3 to 6 carbon atoms.

Examples of the disecondary diamine of the formula (V) may be selectedfrom N,N′-dibenzyl-5-oxanonane diamine-1,9,N,N′-dibenzylethylenediamine, N,N′-dibenzyltrimethylenediamine,N,N′-dibenzylhexamethylenediamine, N,N′-dimethylhexamethylenediamine,N,N′-diethyl-2,2,4-trimethylhexamethylene diamine,N,N′-di(cyclohexyl)-2,4,4-trimethylhexamethylenediamine andN,N′-di(cyclohexyl)hexamethylenediamine.

The dental composition according to the present invention may optionallyfurther contain (c) one or more aliphatic polyamines. The aliphaticpolyamines may contain functional groups such as ether groups, estergroups, or hydroxyl groups. Preferably, an aliphatic polyamine isselected among compounds of the following structures:

whereinR¹⁰ denotes hydrogen or a substituted or unsubstituted C₁ to C₁₈ alkylgroup, a substituted or unsubstituted C₃ to C₁₈ cycloalkyl group, or asubstituted or unsubstituted C₇ to C₁₈ aralkyl group,R²⁰ represents a difunctional substituted or unsubstituted C₁ to C₁₈alkylene group, or a substituted or unsubstituted cycloalkylene group,A′ denotes a moiety derived from a compound that is capable of anaddition reaction with amines such as di- or polyepoxides,c is an integer.

The substituent of the groups of R¹⁰ and R²⁰ may be selected from C₁ toC₁₈ alkyl groups such as a methyl group, an ethyl group, a propyl group,a butyl group, a pentyl group or a hexyl group. The alkyl groups may bestraight chain or branched alkyl groups.

Specific examples of the aliphatic polyamines are selected from JeffaminT403, Jeffamin T3000, and Jeffamin T5000.

Component (c) may be used for improving the curing properties of thedental composition, including the gel time. Accordingly, if present,component (c) is incorporated preferably in an amount of from 5 to 95percent by weight based on the total amount of (b) and (c) in the dentalcomposition of the present invention. According to a preferredembodiment, the gel time of the dental composition of the presentinvention is at most 15 hours, more preferably at most 4 hours and stillmore preferably at most 1 hours.

The dental composition according to the present invention comprises (d)a particulate filler. Preferably, the dental composition of theinvention contains 40 to 85 wt.-% of a filler for providing a minimumradioopacity of the cured composition of at least 3 mm/mm Al. The fillermay contain La₂O₃, ZrO₂, BiPO₄, CaWO₄, BaWO₄, SrF₂, Bi₂O₃. Theradioopacity of the cured composition of the invention is at least 3 mmAl, preferably at least 5 to 7 mm Al, and most preferably at least 7 mmAl.

In the dental composition of the present invention, the molar ratio ofepoxide groups in component (a) to the N—H bonds in component (b) and(c) [epoxide(a)]/[N—H(b),(c)] is in the range of from 0.9 to 1.1.Preferably, the molar ratio is about 1.

Preferably, the dental root canal sealing composition of the inventiondoes not contain a diluent, in particular a reactive diluent. Moreover,the dental composition does not need to contain a polymerisationinitiator. In a preferred embodiment, the dental root canal sealingcomposition consists essentially of components (a), (b) and (d), or (a)to (d). A dental root canal sealing composition consisting essentiallyof components (a), (b) and (d), or (a) to (d) may contain commonadditives used in the dental field such as colorants, antibiotic agentsand ion releasing agents, in a total amount of not more than 25 wt.-%,preferably not more than 10 wt. % of the composition.

The dental root canal sealing composition of the present invention ispreferably a two component composition which is mixed prior to use. Thetwo component composition is preferably a powder/liquid system, apowder/paste system, a paste/paste system or a liquid/paste system. Thepaste/paste system or a liquid/paste system may be applied by anapplicator wherein both components are mixed by a static mixer.

The dental composition of the present invention preferably has aviscosity at 23° C. of less than 100 Pa*s. Preferably, the viscosity ofthe prepolymer is in the range of from 1 to 80 Pa*s, more preferablyfrom 1 to 20 Pa*s. If the viscosity is too high, then it will bedifficult to apply the composition through the canal of a needle. If theviscosity is too low, then it will be difficult handle the composition.

The dental root canal sealing composition of the present invention iscurable in the absence of a polymerisation initiator. The curingmechanism is based on an addition reaction between component (a) andcomponents (b)/(c).

A composition of the present invention may be applied to a root canal byusing conventional techniques. Specifically, the compositions of thepresent invention may be applied via the needle of a syringe into theroot canal.

Moreover, the compositions of the present invention may also be used forthe manufacture of prefabricated root canal cones. If cones made of thecompositions of the invention are used in combination with therespective dental root canal sealing composition of the invention,compatibility of the cones with the sealing composition can beguaranteed whereby a tight seal may be obtained. The cured productobtained with the composition according to the invention has superiormechanical properties, in particular with regard to flexibility, whichis essential for the application as a root canal sealing composition.

EXAMPLES Reference Example 1—AG 19-24-1

A dental root canal sealing material is obtained by mixing homogeneously20.000 g (89.993 mmol) recorcinol diglycidyl ether, 9.644 g (89.993mmol) benzylamine and 70.000 g CaWO₄. This dental material has agelation time of 1.5 hours (at 37° C.) and a radiopacity of 9.4 mm Al.

Reference Example 2—AG 19-24-2

A dental root canal sealing material is obtained by mixing homogeneously5.239 g (23.574 mmol) recorcinol diglycidyl ether, 8.027 g (23.574 mmol)N,N′-dibenzyl-5-oxanonane diamine-1,9 and 35.780 g ZrO₂. This dentalmaterial has a gelation time of 8 hours (at 37° C.) and a radiopacity of10.1 mm Al.

Reference Example 3—AG 19-24-3

A dental root canal sealing material is obtained by mixing homogeneously12.230 g (55.031 mmol) recorcinol diglycidyl ether, 13.227 g (55.031mmol) N,N′-dibenzylethylenediamine and 35.780 g CaWO₄. This dentalmaterial has a gelation time of 6 hours (at 37° C.) and a radiopacity of6.1 mm/mm Al.

Reference Example 4—AG 19-24-4

A dental root canal sealing material is obtained by mixing homogeneously9.300 g (33.422 mmol) phthalic acid diglycidylester, 11.381 g (33.422mmol) N,N′-dibenzyl-5-oxanonane diamine-1,9 and 62.300 g CaWO₄. Thisdental material has a gelation time of 20 hours (at 37° C.) and aradiopacity of 10.4 mm Al.

Example 5—AG

A dental root canal sealing material is obtained by mixing homogeneously2.000 g (8.999 mmol) recorcinol diglycidyl ether, 0.182 g (0.900 mmol)butanediol diglycidylether, 3.371 g (9.899 mmol)N,N′-dibenzyl-5-oxanonane diamine-1,9 and 32.000 g CaWO₄. This dentalmaterial has a setting time of 13 hours (at 37° C.) and a radiopacity of16.0±0.4 mm/mm Al.

Example 6—AG

A dental root canal sealing material is obtained by mixing homogeneously2.000 g (8.999 mmol) recorcinol diglycidyl ether, 1.820 g (8.999 mmol)butanediol diglycidylether, 6.129 g (17.999 mmol)N,N′-dibenzyl-5-oxanonane diamine-1,9 and 65.000 g CaWO₄. This dentalmaterial has a setting time of 19 hours (at 37° C.) and a radiopacity of15.9±0.1 mm/mm Al.

All of the commercially available root canal sealers basing onepoxide-amine chemistry contain Bisphenol-A diglycidylether (DGEBA): AHPlus (DENTSPLY), AH 26 (DENTSPLY), Asphaline (Alfred Becht GmbH),Acroseal (Septodont), Adseal (META BIOMED), Perma Evolution (METABIOMED), EZ-Fill (Essentail Dental Systems).

The radiopacity of all samples was measured according to ISO 6876:2012.

1. Dental composition comprising (a) at least two di- or polyepoxideshaving 2 to 5 epoxide groups and having a molecular weight of from 200to 700 Da, or a macromonomeric reaction product obtainable by reactingthe diepoxide with a dicarboxylic acid in a molar ratio[diepoxide]/[dicarboxylic acid] of at least 2; (b) one or more primarymonoamines and/or disecondary diamines; (c) optionally one or morealiphatic polyamines; (d) a particulate filler, wherein the molar ratioof epoxide groups in component (a) to the N—H bonds in component (b) and(c) [epoxide_((a))]/[N—H_((b),(c))] is in the range of from 0.9 to 1.1;wherein the di- or polyepoxide having 2 to 5 epoxide groups is acompound of the following formula (I):A(BZ_(m))_(n)  (I) wherein A represents an n-valent organic moietyoptionally having 1 to 10 heteroatoms selected from oxygen atoms andsulfur atoms; and B represents an m+1-valent organic moiety, Z is anepoxide group which may have a substituent, m which are independent fromeach other represent an integer of at least 1; and n is an integer offrom 1 to 5; wherein the m are selected so that 2 to 5 epoxide groupsare present; wherein the composition does not contain any2,2-bis-(4-hydroxyphenyl)-propane or 2,2-bis-(4-hydroxyphenyl)-methane.2. The dental composition according to claim 1, wherein component (c) ispresent in an amount of from 5 to 95 percent by weight based on thetotal amount of (b) and (c) in the composition.
 3. The dentalcomposition according to claim 1 or 2, wherein component (c) is analiphatic polyamine selected among compounds of the followingstructures:

wherein R¹⁰ denotes hydrogen or a substituted or unsubstituted C₁ to C₁₈alkyl group, a substituted or unsubstituted C₃ to C₁₈ cycloalkyl group,or a substituted or unsubstituted C₇ to C₁₈ aralkyl group, R²⁰represents a difunctional substituted or unsubstituted C₁ to C₁₈alkylene group, or a substituted or unsubstituted cycloalkylene group,A′ denotes a moiety derived from a compound that is capable of anaddition reaction with amines such as di- or polyepoxides, c is aninteger.
 4. The dental composition according to any one of the precedingclaims, wherein the heteroatoms selected from oxygen atoms and sulfuratoms in groups A are present in ester bonds, ether bonds, thioetherbonds or thioester bonds.
 5. The dental composition according to any oneof the preceding claims, wherein A contains an aromatic ring.
 6. Thedental composition according to any one of the preceding claims, whereinthe at least two di- or polyepoxides having 2 to 5 epoxide groups areobtainable by reacting a compound having 2 to 5 hydroxyl groups withepichlorohydrine.
 7. The dental composition according to claim 6,wherein the compound having 3 to 5 hydroxyl groups contains phenolichydroxyl groups.
 8. The dental composition according to claim 1, whereinBZ is a group of the formula (II) or (III):

wherein X is —NH—, an oxygen atom or a sulfur atom, X′ is —NH—, anoxygen atom or a sulfur atom, X″ is —NH—, an oxygen atom or a sulfuratom, X′″ is —CH₂—, —NH—, an oxygen atom or a sulfur atom, R¹¹ and R¹²which may be the same or different, independently represent a hydrogenatom or a straight chain or branched C₁₋₆ alkyl group, R¹³ represents ahydrogen atom or a straight chain or branched C₁₋₆ alkyl group, R¹⁴represents a hydrogen atom, a hydroxyl group which may be substituted,or a straight chain or branched C₁₋₆ alkyl group, o represents aninteger of from 2 to 10, p is an integer of from 0, 1 or 2; q which maybe the same or different, independently represent an integer of from 0to 10; v represents an integer of from 1 to
 10. 9. The dentalcomposition according to any one of the preceding claims, which is aroot canal filling composition or a pulp capping composition.
 10. Thedental composition according to any one of the preceding claims, whichhas a gel time of at most 12 hours.
 11. A process for preparing acomposition according to any one of claims 1 to 10, which comprisesreacting one or more compounds having 2 to 5 hydroxyl groups withepichlorohydrine for preparing a di- or polyepoxide having 2 to 5epoxide groups as defined by claim
 1. 12. The process according to claim11, which further comprises a step reacting the diepoxide with adicarboxylic acid in a molar ratio [diepoxide]/[dicarboxylic acid] of atleast 2 for obtaining a macromonomeric reaction product.
 13. Di- orpolyepoxide having 2 to 5 epoxide groups obtainable by the processaccording to any one of claim 11 or 12.